Fig. 9: Model of lifespan and metabolic differences in sterile germline mutants.

Feminized fem-3(e1996) mutants are long-lived, though not as long as the well-characterized germline-less glp-1(e2144) mutants, while masculinized mog-3(q74) mutants are short-lived. All three sterile mutants—glp-1(e2144), fem-3(e1996), and mog-3(q74)—accumulate excess neutral lipids, activate SKN-1, show transcriptional upregulation of stress response genes, and display enhanced resistance to Pseudomonas aeruginosa (PA14) infection. Integrated lipidomic and transcriptomic analyses reveal distinct sphingolipid metabolic signatures across these genotypes. Notably, sphingosine levels are lower in the long-lived glp-1(e2144) and fem-3(e1996) mutants but elevated in the short-lived mog-3(q74) mutant. Interestingly, DAF-16 is activated only in the long-lived glp-1(e2144) and fem-3(e1996) mutants, which likely contributes to their extended longevity. While the sphingosine level differences correlate with lifespan outcomes, it should not be implied that sphingolipid changes act upstream of SKN-1 or DAF-16. mog-3(q74) mutants closely resemble mated hermaphrodites and exhibit features of male/mating-induced demise (MID), which likely accounts for their shortened lifespan. (Created in BioRender. Lee, S. (2025) https://BioRender.com/z7nn034).